Figure 1

Scales characterizing bioavailability studies. Any feature or property of a specific study subject following dosing (the system) can be characterized by an approximate location on both scales. Uncertainty example: we know very little about the likely state of the extended release dosage in a particular subject at a particular time after dosing. Consequently, for that feature, we are left of center on the Uncertainty Scale. Mechanistic knowledge: we know very little about the actual mechanisms responsible for differences in drug plasma profiles. Consequently, here too, we are on the left side of the scale. We need plausible mechanisms that can explain the large intra- and interindividual variability in bioavailability.